E-selectin receptors on human leukocytes

Blood. 2008 Nov 1;112(9):3744-52. doi: 10.1182/blood-2008-04-149641. Epub 2008 Jun 25.


Selectins on activated vascular endothelium mediate inflammation by binding to complementary carbohydrates on circulating neutrophils. The human neutrophil receptor for E-selectin has not been established. We report here that sialylated glycosphingolipids with 5 N-acetyllactosamine (LacNAc, Galbeta1-4GlcNAcbeta1-3) repeats and 2 to 3 fucose residues are major functional E-selectin receptors on human neutrophils. Glycolipids were extracted from 10(10) normal peripheral blood human neutrophils. Individual glycolipid species were resolved by chromatography, adsorbed as model membrane monolayers and selectin-mediated cell tethering and rolling under fluid shear was quantified as a function of glycolipid density. E-selectin-expressing cells tethered and rolled on selected glycolipids, whereas P-selectin-expressing cells failed to interact. Quantitatively minor terminally sialylated glycosphingolipids with 5 to 6 LacNAc repeats and 2 to 3 fucose residues were highly potent E-selectin receptors, constituting more than 60% of the E-selectin-binding activity in the extract. These glycolipids are expressed on human blood neutrophils at densities exceeding those required to support E-selectin-mediated tethering and rolling. Blocking glycosphingolipid biosynthesis in cultured human neutrophils diminished E-selectin, but not P-selectin, adhesion. The data support the conclusion that on human neutrophils the glycosphingolipid NeuAcalpha2-3Galbeta1-4GlcNAcbeta1-3[Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-3](2)[Galbeta1-4GlcNAcbeta1-3](2)Galbeta1-4GlcbetaCer (and closely related structures) are functional E-selectin receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Sugars / chemistry
  • Carbohydrate Sequence
  • Cell Adhesion
  • E-Selectin / blood*
  • Fucose / chemistry
  • Gangliosides / blood*
  • Gangliosides / chemistry
  • Gangliosides / isolation & purification
  • Humans
  • In Vitro Techniques
  • Leukocyte Rolling
  • Leukocytes / metabolism*
  • Molecular Sequence Data
  • Molecular Structure
  • Neutrophils / metabolism
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Amino Sugars
  • E-Selectin
  • Gangliosides
  • Fucose
  • N-acetyllactosamine